Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells.
The CD11b/CD18 integrin (complement receptor 3, CR3) is a surface receptor on monocytes, neutrophils, macrophages and dendritic cells that plays a crucial role in several immunological processes including leukocyte extravasation and phagocytosis. The minor allele of a non-synonymous CR3 polymorphism...
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0057082&type=printable |
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| author | Liliane Fossati-Jimack Guang Sheng Ling Andrea Cortini Marta Szajna Talat H Malik Jacqueline U McDonald Matthew C Pickering H Terence Cook Philip R Taylor Marina Botto |
| author_facet | Liliane Fossati-Jimack Guang Sheng Ling Andrea Cortini Marta Szajna Talat H Malik Jacqueline U McDonald Matthew C Pickering H Terence Cook Philip R Taylor Marina Botto |
| author_sort | Liliane Fossati-Jimack |
| collection | DOAJ |
| description | The CD11b/CD18 integrin (complement receptor 3, CR3) is a surface receptor on monocytes, neutrophils, macrophages and dendritic cells that plays a crucial role in several immunological processes including leukocyte extravasation and phagocytosis. The minor allele of a non-synonymous CR3 polymorphism (rs1143679, conversation of arginine to histidine at position 77: R77H) represents one of the strongest genetic risk factor in human systemic lupus erythematosus, with heterozygosity (77R/H) being the most common disease associated genotype. Homozygosity for the 77H allele has been reported to reduce adhesion and phagocytosis in human monocytes and monocyte-derived macrophages, respectively, without affecting surface expression of CD11b. Herein we comprehensively assessed the influence of R77H on different CR3-mediated activities in monocytes, neutrophils, macrophages and dendritic cells. R77H did not alter surface expression of CD11b including its active form in any of these cell types. Using two different iC3b-coated targets we found that the uptake by heterozygous 77R/H macrophages, monocytes and neutrophils was significantly reduced compared to 77R/R cells. Allele-specific transduced immortalized macrophage cell lines demonstrated that the minor allele, 77H, was responsible for the impaired phagocytosis. R77H did not affect neutrophil adhesion, neutrophil transmigration in vivo or Toll-like receptor 7/8-mediated cytokine release by monocytes or dendritic cells with or without CR3 pre-engagement by iC3b-coated targets. Our findings demonstrate that the reduction in CR3-mediated phagocytosis associated with the 77H CD11b variant is not macrophage-restricted but demonstrable in other CR3-expressing professional phagocytic cells. The association between 77H and susceptibility to systemic lupus erythematosus most likely relates to impaired waste disposal, a key component of lupus pathogenesis. |
| format | Article |
| id | doaj-art-e63a8310893d443fa4d86f29715bc0ea |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e63a8310893d443fa4d86f29715bc0ea2025-08-20T03:25:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5708210.1371/journal.pone.0057082Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells.Liliane Fossati-JimackGuang Sheng LingAndrea CortiniMarta SzajnaTalat H MalikJacqueline U McDonaldMatthew C PickeringH Terence CookPhilip R TaylorMarina BottoThe CD11b/CD18 integrin (complement receptor 3, CR3) is a surface receptor on monocytes, neutrophils, macrophages and dendritic cells that plays a crucial role in several immunological processes including leukocyte extravasation and phagocytosis. The minor allele of a non-synonymous CR3 polymorphism (rs1143679, conversation of arginine to histidine at position 77: R77H) represents one of the strongest genetic risk factor in human systemic lupus erythematosus, with heterozygosity (77R/H) being the most common disease associated genotype. Homozygosity for the 77H allele has been reported to reduce adhesion and phagocytosis in human monocytes and monocyte-derived macrophages, respectively, without affecting surface expression of CD11b. Herein we comprehensively assessed the influence of R77H on different CR3-mediated activities in monocytes, neutrophils, macrophages and dendritic cells. R77H did not alter surface expression of CD11b including its active form in any of these cell types. Using two different iC3b-coated targets we found that the uptake by heterozygous 77R/H macrophages, monocytes and neutrophils was significantly reduced compared to 77R/R cells. Allele-specific transduced immortalized macrophage cell lines demonstrated that the minor allele, 77H, was responsible for the impaired phagocytosis. R77H did not affect neutrophil adhesion, neutrophil transmigration in vivo or Toll-like receptor 7/8-mediated cytokine release by monocytes or dendritic cells with or without CR3 pre-engagement by iC3b-coated targets. Our findings demonstrate that the reduction in CR3-mediated phagocytosis associated with the 77H CD11b variant is not macrophage-restricted but demonstrable in other CR3-expressing professional phagocytic cells. The association between 77H and susceptibility to systemic lupus erythematosus most likely relates to impaired waste disposal, a key component of lupus pathogenesis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0057082&type=printable |
| spellingShingle | Liliane Fossati-Jimack Guang Sheng Ling Andrea Cortini Marta Szajna Talat H Malik Jacqueline U McDonald Matthew C Pickering H Terence Cook Philip R Taylor Marina Botto Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells. PLoS ONE |
| title | Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells. |
| title_full | Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells. |
| title_fullStr | Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells. |
| title_full_unstemmed | Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells. |
| title_short | Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells. |
| title_sort | phagocytosis is the main cr3 mediated function affected by the lupus associated variant of cd11b in human myeloid cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0057082&type=printable |
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